Expanding Organ Preservation in Locally Advanced Rectal Cancer After Total Neoadjuvant Therapy with Endoscopic Submucosal Dissection

Background: In the management of locally advanced rectal cancer, organ preservation after total neoadjuvant therapy requires complete clinical response and close surveillance. Patients with near complete response or tumor regrowth during watch and wait are recommended to undergo total mesorectal excision. Selective use of local resection procedures, such as endoscopic submucosal dissection, may expand organ preservation in these patients. Objective: To assess the feasibility, safety and outcomes of endoscopic submucosal dissection for patients with near-complete response or tumor regrowth after total neoadjuvant therapy. Design: Retrospective cohort study. Settings: Single tertiary care center. Patients: Patients with locally advanced rectal cancer treated with total neoadjuvant therapy between 2015 and 2024, who underwent endoscopic submucosal dissection for near-complete response or tumor regrowth during active surveillance. Interventions: Endoscopic submucosal dissection for near-complete response and tumor regrowth during watch-and-wait. Main Outcome Measures: Organ preservation and regrowth rates following endoscopic submucosal dissection. Results: Twenty patients were included (40% female, mean age 59.1 ± 13.1 years). While 10 patients underwent endoscopic submucosal dissection for near-complete response with endoluminal lesions following total neoadjuvant therapy completion, 10 underwent endoscopic submucosal dissection due to tumor regrowth during watch-and-wait. The median time for tumor regrowth was 12.5 months. Pathologic examination of specimens showed no invasive cancer in 14 patients (70%). Total mesorectal excision was performed in five patients due to the invasive adenocarcinoma found on endoscopic submucosal dissection. The other patient refused proctectomy. One patient with dysplasia, following an additional Watch & Wait period after endoscopic submucosal dissection, underwent total mesorectal excision due to second regrowth. Fourteen patients, including the one who refused surgery, have been closely monitored to date, with no evidence of disease for a mean of 27.7 months. Limitations: Retrospective design and small sample size. Conclusion: Selective use of endoscopic submucosal dissection can be feasible and safe for organ preservation in highly selected patients with locally advanced rectal cancer following total neoadjuvant therapy. Larger prospective trials with longer follow-up are needed to validate its value. See Video Abstract.